Osteoporosis

Until recently, it was assumed that the only interaction between muscle and bone is mechanical, that the muscle acts as a pulley and the bone as a lever to move the organism. A relatively new concept is that muscle, especially contracted muscle, acts as a secretory organ, regulating metabolism. An even newer concept is that bone, especially the osteocytes in bone, act as endocrine cells targeting other organs such as kidney and more recently, muscle. These two new concepts logically led to the third concept: that muscle and bone communicate via soluble factors...

New England Journal of Medicine, Volume 379, Issue 25, Page 2465-2466, December 2018.

The prevalence of fragility fractures increases as longevity increases the proportion of the elderly in the community. Until recently, the majority of studies have targeted women with osteoporosis defined as a bone mineral density (BMD) T score of < -2.5 SD, despite evidence that the population burden of fractures arises from women with osteopenia. Antiresorptive agents reduce vertebral and hip fracture risk by ~50 percent during 3 years but efficacy against non-vertebral fractures, 80% of all fractures in the community, is reported in few studies, and of those, the risk reduction is only 20-30%...

Medications for osteoporosis are classified as either antiresorptive or anabolic. Whereas antiresorptive agents prevent bone resorption, anabolic agents promote new bone formation. Anabolics should be considered in individuals with severe osteoporosis, failure of alternative osteoporosis agents, intolerability or contraindications to other osteoporosis agents, and glucocorticoid-induced osteoporosis. There are currently two approved anabolic therapies, teriparatide and abaloparatide, and a third anabolic agent, romozosumab, is under review by the US Food and Drug Administration...

BACKGROUND: Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management. METHODS: In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease...

Methods for preventing medication-related osteonecrosis of the jaw (MRONJ) in cancer patients who have received high-dose bisphosphonate (BP) or denosumab (Dmab) have not yet been established. Tooth extraction after starting medication has been believed to be a major risk factor for MRONJ, and therefore this procedure tends to be avoided. This study investigated the risk factors for MRONJ, with a special reference to the correlation between tooth extraction and development of MRONJ. One hundred and thirty-five cancer patients who were administrated high-dose BP or Dmab were enrolled in the study...

BACKGROUND: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking. OBJECTIVE: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans...

PURPOSE OF REVIEW: To summarize reports published since the 2013 American Society of Bone and Mineral Research Task Force Report on atypical femoral fractures (AFF). RECENT FINDINGS: The absolute incidence of AFFs remains low. AFFs are primarily associated with prolonged bisphosphonate (BP) exposure, but have also been reported in unexposed patients and those receiving denosumab for osteoporosis and metastatic bone disease. Asians may be more susceptible to AFFs...

CONTEXT: Globally, one in five men aged >50 years is predicted to experience an osteoporotic fracture. Because of the treatment gap in osteoporosis and the paucity of bone-forming agents for men, new osteoporosis treatments are needed. OBJECTIVE: To evaluate the safety and efficacy of romosozumab in men with osteoporosis. DESIGN: Phase III randomized BRIDGE study (placebo-controlled double-blind study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis; ClinicalTrials...

Modern Western diets, with higher contents of animal compared to fruits and vegetable products, have a greater content of acid precursors vs. base precursors, which results in a net acid load to the body. To prevent inexorable accumulation of acid in the body and progressively increasing degrees of metabolic acidosis, the body has multiple systems to buffer and titrate acid, including bone which contains large quantities of alkaline salts of calcium. Both in vitro and in vivo studies in animals and humans suggest that bone base helps neutralize part of the dietary net acid load...

Background: While it is well known that teriparatide (TPTD) increases bone mineral density (BMD) in osteoporotic patients, it is unknown whether TPTD pretreatment affects BMD after denosumab (DMAb) therapy. Methods: Fifty-seven patients in TPTD-pretreated group and 35 patients in DMAb-alone group had been further analyzed, all of whom were treated by DMAb for 1.5 years. Vitamin D (400 IU) and Ca (600 mg) supplementation was used in all patients. The BMD of lumbar 1-4 vertebrae (L-BMD), bilateral total hips (H-BMD), and bilateral femoral neck (FN-BMD) was quantified at first visit, and at 4, 8, 12, and 18 months after daily TPTD treatment following four times DMAb treatment...

Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months...

The aim of the present study was to document the changes in bone mineral density (BMD) 1 year after denosumab loss-of-effect following long-term treatment with subcutaneous denosumab 60 mg Q6M during 7 or 10 years and in the absence of any treatment with a bone active substance. All postmenopausal women with osteoporosis who participated to the randomized placebo-controlled FREEDOM core trial and its open-label extension at the University Hospital of Bern, Switzerland, and who accepted to undergo off-treatment follow-up during 1 year after discontinuation, were included (N = 12)...

The regular consumption of long-chain omega-3 polyunsaturated fatty acids (LCO3-PUFAs) results in general health benefits. The intake of LCO3-PUFAs has been reported to contribute to bone metabolism. We aimed to investigate the relationships between dietary intakes of LCO3-PUFAs and bone mineral density (BMD) in Spanish women aged 20-79 years old. A total of 1865 female subjects (20-79 years old) were enrolled, and lumbar (L2, L3, L3 and total spine), hip (femoral neck (FN), femoral trochanter (FT) and Ward's triangle (WT)) bone mineral density (BMD) were measured by dual energy X-ray absorptiometry (DXA)...

Denosumab, a human monoclonal antibody against RANK ligand, is shown to have strong anti-fracture effects in Japanese osteoporosis patients. However, there have been no data showing actions on Japanese bone architecture. Here we show that denosumab continuously improves several geometrical parameters calculated by hip structural analysis for 3 years. Compared to placebo, denosumab significantly increased bone mineral density, cortical thickness and cross sectional area in all of the three analyzed areas: the narrow neck, intertrochanter and femoral shaft...

INTRODUCTION: Irisin is a myokine/adipokine induced by the exercise in mice and humans, which is proposed to induce "browning" of white adipose tissue, its primary target, thus increasing thermogenesis and energy expenditure. Since its identification, irisin has been linked to favorable effects on metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), lipid metabolism and cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic bone diseases...

OBJECTIVES: To determine, in conjunction with a wider investigation, whether 11 genetic variants in the vicinity of vitamin D, collagen and Wnt signalling pathways were associated with stress fracture injury in the Stress Fracture Elite Athlete (SFEA) cohort. DESIGN: Genotype-phenotype association study. METHODS: Self-reported stress fracture history and demographic data were recorded in 518 elite athletes, 449 male and 69 female (mean age 24...

Objective: The meta-analysis was used to evaluate the skeletal-related events (SREs) and efficacy of denosumab versus zoledronic acid (ZA) in patients with bone metastases. Methods: The data of this meta-analysis study were searched from PUBMED, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier and China National Knowledge Infrastructure (CNKI) databases till August 2017. Two independent reviewers reviewed the reference lists of relevant articles...

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts...

Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors...